Congenital cutaneous neurofibromas in neurofibromatosis type 1: Clinicopathological features in early infancy

Background and objective: Clinicopathological features of cutaneous neurofibromas presenting as large irregularly shaped congenital cafe-au-lait macules (CALM) in Neurofibromatosis type 1 (NF1) patients have not been well characterized. We aimed to analyze the histopathological findings of large "atypical" CALM in children with NF1. Patients and Methods: In this retrospective observational study we analyzed histopathological and immunostaining features of 21 biopsy specimens from 18 large hyperpigmented macules with irregular borders with or without hypertrichosis present during the first months of life in NF1 diagnosed children. Results: Of the 21 biopsies, ten showed a diffuse neurofibroma pattern and four exhibited characteristics of plexiform neurofibroma (PNF). In twelve specimens we observed groups of fusiform cells arranged linearly mimicking a small caliber nerve trunk with abnormal morphology. Repeated biopsies from two of these lesions performed at different ages showed transformation to a plexiform pattern. An increased interstitial cellularity was observed in 17 samples that was more evident around eccrine glands in 16 or accompanying hair follicles and vascular structures in twelve samples. All these cells had immunoreactivity for S100-protein, CD68 and were Melan-A positive in 15 samples. Conclusion: Clinicopathological findings of congenital cutaneous neurofibromas provide early diagnostic clues of NF1 with high relevance for monitoring of these patients.